EP0338898B1 - Process for the preparation of an ortho-substituted mono-brominated derivative of phenol - Google Patents

Process for the preparation of an ortho-substituted mono-brominated derivative of phenol Download PDF

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Publication number
EP0338898B1
EP0338898B1 EP89401027A EP89401027A EP0338898B1 EP 0338898 B1 EP0338898 B1 EP 0338898B1 EP 89401027 A EP89401027 A EP 89401027A EP 89401027 A EP89401027 A EP 89401027A EP 0338898 B1 EP0338898 B1 EP 0338898B1
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Prior art keywords
derivative
phenol
ortho
formula
radical
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EP89401027A
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German (de)
French (fr)
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EP0338898A1 (en
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Jean-Roger Desmurs
Isabelle Jouve
Alain Nonn
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Rhodia Chimie SAS
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Rhone Poulenc Chimie SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms

Definitions

  • the present invention relates to the preparation of a mono-brominated ortho derivative of the phenol of formula: in which X represents OH, an alkoxy radical, CH2OH, CHO, CO2R, R being an alkyl, alkenyl or alkyloxy radical, these radicals being able to be linear or branched, cycloalkyl, cycloalkenyl, alkylcycloalkenyl, benzyl, amine, terpene, glycolic, R1 and R2 are the same or different and represent hydrogen, a halogen, an alkyl, acyl or alkoxy radical and with the condition that the ortho position of the OH is free, this preparation being made from the product of formula (1) X, R1 and R2 being as previously defined.
  • the main object of the invention is therefore a process allowing this monobromation in ortho with an acceptable yield.
  • the Applicant has realized that the problem could be resolved by using a specific brominating agent.
  • the process according to the invention for the preparation of a mono-brominated derivative ortho to phenol is characterized in that a phenol derivative of formula is reacted in which X represents OH, an alkoxy radical, CH2OH, CHO, CO2R, R being an alkyl, alkenyl or alkyloxy radical, these radicals being able to be linear or branched, cycloalkyl, cycloalkenyl, alkylcycloalkenyl, benzyl, amine, terpene, glycolic, R1 and R2 are the same or different and represent hydrogen, a halogen, an alkyl, acyl or alkoxy radical and with the condition that the ortho position of the OH an alkoxy radical is free with an amine derivative having at least one N bond -Br.
  • the starting product is a phenol derivative corresponding to formula 1 given above.
  • the invention applies particularly well to products for which R1 and R2 are in the meta position and also to those for which R1 and R2 both represent hydrogen.
  • salicylates can also be mentioned, that is to say the products for which X in formula (1) is a CO2R radical, R being as defined above.
  • R1 and R2 are both hydrogen and in particular the salicylates of n-hexyl, benzyl, methyl, amyl, isoamyl and 2-ethyl hexyl, cis-hexen-3 yl-1, glycol, prenyl, 2-ethyl butyl, 2-methyl pentyl, monomethylamine, 3,3,5 trimethyl cyclohexyl, 2-isopropyl cyclohexyl, beta-isopropoxyethyl, bornyl.
  • the brominating agent with which the compound of formula 1 is reacted is a brominated derivative of an amine.
  • the aliphatic amines and in particular the alkylamines are chosen more especially.
  • the brominated derivatives of formulas RNHBr, RNBr2 or RR′NBr for which R and / or R ′ represent a methyl, ethyl, isopropyl, isobutyl, cyclohexyl and more particularly tert-butyl radical may be mentioned.
  • the reaction is carried out in a solvent medium.
  • solvent it is possible to use halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated or not, ethers.
  • ethers mention may be made more particularly of isopropyl ether, butyl oxide, hexyl oxide.
  • the reaction is generally carried out at a temperature close to 0 ° C.
  • the concentration of phenol derivative (starting product) is usually between 0.1 and 10 moles / l.
  • an amount of brominating agent is used between 0.8 and 1.2 equivalent of reactive bromine.
  • the reaction is carried out in principle by pouring the brominating agent into the solvent-phenol derivative mixture.
  • the product can be separated from the reaction medium by any known means after, if necessary, conventional treatment for the transition from its salt form to the desired form.
  • An example of treatment consists in adding an acid solution to the reaction medium and in increasing the temperature in order to hydrolyze the precipitate formed during the reaction.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Macromonomer-Based Addition Polymer (AREA)
  • Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)

Abstract

This process is characterised in that a phenol derivative of formula: <IMAGE> in which X denotes OH, an alkoxy, CH2OH, CHO or CO2R radical, R1 and R2 are identical or different and denote hydrogen, a halogen, an alkyl, acyl or alkoxy radical and provided that the position ortho to the OH is free, is reacted with an amine derivative containing at least one N-Br bond.

Description

La présente invention concerne la préparation d'un dérivé mono-bromé en ortho du phénol de formule :

Figure imgb0001

dans laquelle X représente OH,un radical alcoxy, CH₂OH, CHO, CO₂R, R étant un radical alkyle, alcényle, alkyloxy, ces radicaux pouvant être linéaire ou ramifiés, cycloalkyle, cycloalcényle, alkylcycloalcényle, benzyle, amine, terpénique, glycolique, R₁ et R₂ sont identiques ou différents et représentent l'hydrogène, un halogène, un radical alkyle, acyle ou alcoxy et avec comme condition que la position en ortho du OH soit libre, cette préparation se faisant à partir du produit de formule (1)
Figure imgb0002
X, R₁ et R₂ etant tels que précédemment définis.The present invention relates to the preparation of a mono-brominated ortho derivative of the phenol of formula:
Figure imgb0001
in which X represents OH, an alkoxy radical, CH₂OH, CHO, CO₂R, R being an alkyl, alkenyl or alkyloxy radical, these radicals being able to be linear or branched, cycloalkyl, cycloalkenyl, alkylcycloalkenyl, benzyl, amine, terpene, glycolic, R₁ and R₂ are the same or different and represent hydrogen, a halogen, an alkyl, acyl or alkoxy radical and with the condition that the ortho position of the OH is free, this preparation being made from the product of formula (1)
Figure imgb0002
X, R₁ and R₂ being as previously defined.

Le problème qui se pose pour la bromation de tels produits est double. On veut d'une part obtenir un dérivé monobromé et non pas dibromé. D'autre part, cette bromation doit être regio-sélective car on désire former essentiellement le dérivé bromé en ortho. On peut indiquer à ce sujet qu'une bromation d'un produit tel que le gaïacol par le brome donne 80 % de dérivé bromé en para et 20 % de dérivé bromé en ortho seulement.The problem which arises for the bromination of such products is twofold. On the one hand, we want to obtain a monobrominated and not dibromed derivative. On the other hand, this bromination must be regio-selective because it is desired to essentially form the brominated derivative in ortho. We can indicate on this subject that bromination of a product such as guaiacol by bromine gives 80% of brominated derivative in para and 20% of brominated derivative in ortho only.

L'objet principal de l'invention est donc un procédé permettant cette monobromation en ortho avec un rendement acceptable. Or, la Demanderesse s'est aperçu que le problème pouvait être résolu en utilisant un agent bromant spécifique.The main object of the invention is therefore a process allowing this monobromation in ortho with an acceptable yield. However, the Applicant has realized that the problem could be resolved by using a specific brominating agent.

Dans ce but, le procédé selon l'invention de préparation d'un dérivé mono-bromé en ortho du phénol est caractérisé en ce qu'on fait réagir un dérivé du phénol de formule

Figure imgb0003

dans laquelle X représente OH, un radical alcoxy, CH₂OH, CHO, CO₂R, R étant un radical alkyle, alcényle, alkyloxy, ces radicaux pouvant être linéaires ou ramifiés, cycloalkyle, cycloalcényle, alkylcycloalcényle, benzyle, amine, terpénique, glycolique, R₁ et R₂ sont identiques ou différents et représentent l'hydrogène, un halogène, un radical alkyle, acyle ou alcoxy et avec comme condition que la position en ortho du OH un radical alcoxy soit libre avec un dérivé d'une amine présentant au moins une liaison N-Br.For this purpose, the process according to the invention for the preparation of a mono-brominated derivative ortho to phenol is characterized in that a phenol derivative of formula is reacted
Figure imgb0003
in which X represents OH, an alkoxy radical, CH₂OH, CHO, CO₂R, R being an alkyl, alkenyl or alkyloxy radical, these radicals being able to be linear or branched, cycloalkyl, cycloalkenyl, alkylcycloalkenyl, benzyl, amine, terpene, glycolic, R₁ and R₂ are the same or different and represent hydrogen, a halogen, an alkyl, acyl or alkoxy radical and with the condition that the ortho position of the OH an alkoxy radical is free with an amine derivative having at least one N bond -Br.

Dans ces conditions, on obtient un dérivé monobromé en ortho avec un rendement d'au moins 60 %.Under these conditions, a monobromo derivative in ortho is obtained with a yield of at least 60%.

D'autres caractéristiques, détails et avantages de l'invention seront mieux compris à la lecture de la description et d'un exemple concret qui vont suivre.Other characteristics, details and advantages of the invention will be better understood on reading the description and a concrete example which will follow.

Le produit de départ est un dérivé du phénol répondant à la formule 1 donnée ci-dessus.The starting product is a phenol derivative corresponding to formula 1 given above.

L'invention s'applique particulièrement bien aux produits pour lesquels R₁ et R₂ sont en position méta et aussi à ceux pour lesquels R₁ et R₂ représentent tous les deux l'hydrogène.The invention applies particularly well to products for which R₁ and R₂ are in the meta position and also to those for which R₁ and R₂ both represent hydrogen.

On notera, que comme produit de départ particulièrement intéressant on peut utiliser ceux pour lesquels X est un radical alcoxy, et entre autres ceux pour lesquels R₁ et R₂ sont l'hydrogène, notamment parmi ceux-ci le gaïacol (X = OCH₃).It will be noted that, as a particularly advantageous starting product, it is possible to use those for which X is an alkoxy radical, and inter alia those for which R₁ and R₂ are hydrogen, in particular among these guaiacol (X = OCH₃).

Comme autres produits de départ interessants, on peut mentionner aussi les salicylates, c'est-à-dire les produits pour lesquels X dans la formule (1) est un radical CO₂R, R étant tel que défini plus haut.As other interesting starting materials, salicylates can also be mentioned, that is to say the products for which X in formula (1) is a CO₂R radical, R being as defined above.

On peut citer à titre d'exemple les produits pour lesquels R₁ et R₂ sont tous les deux l'hydrogène et notamment les salicylates de n-hexyle, de benzyle, de méthyle, d'amyle, d'isoamyle, d'éthyl-2 hexyle, de cis-hexen-3 yle-1, de glycol, de prenyle, d'éthyl-2 butyle, de méthyl-2 pentyle, de monométhylamine, de triméthyl 3,3,5 cyclohexyle, d'isopropyl-2 cyclohexyle, de béta-isopropoxyéthyle, de bornyle.By way of example, mention may be made of the products for which R₁ and R₂ are both hydrogen and in particular the salicylates of n-hexyl, benzyl, methyl, amyl, isoamyl and 2-ethyl hexyl, cis-hexen-3 yl-1, glycol, prenyl, 2-ethyl butyl, 2-methyl pentyl, monomethylamine, 3,3,5 trimethyl cyclohexyl, 2-isopropyl cyclohexyl, beta-isopropoxyethyl, bornyl.

Comme on l'a vu plus haut, l'agent bromant avec lequel on fait réagir le composé de formule 1 est un dérivé bromé d'une amine. On choisit plus spécialement les amines aliphatiques et en particulier les alkylamines. Les dérivés bromés de formules RNHBr, RNBr₂ ou RR′NBr pour lesquelles R et/ou R′ représentent un radical méthyle, éthyle, isopropyle, isobutyle, cyclohexyle et plus particulièrement tertiobutyle peuvent être citées.As seen above, the brominating agent with which the compound of formula 1 is reacted is a brominated derivative of an amine. The aliphatic amines and in particular the alkylamines are chosen more especially. The brominated derivatives of formulas RNHBr, RNBr₂ or RR′NBr for which R and / or R ′ represent a methyl, ethyl, isopropyl, isobutyl, cyclohexyl and more particularly tert-butyl radical may be mentioned.

La réaction est conduite en milieu solvant. Comme solvant on pourra utiliser les hydrocarbures aliphatiques halogénés, les hydrocarbures aromatiques halogénés ou non, les éthers.The reaction is carried out in a solvent medium. As solvent, it is possible to use halogenated aliphatic hydrocarbons, aromatic hydrocarbons, halogenated or not, ethers.

On peut citer à ce sujet le tétrachlorure de carbone, le dichlorométhane, le chloroéthane, le dichlorobenzène.Mention may be made in this connection of carbon tetrachloride, dichloromethane, chloroethane, dichlorobenzene.

Pour les éthers, on peut mentionner plus particulièrement l'éther isopropylique, l'oxyde de butyle, l'oxyde d'hexyle.For ethers, mention may be made more particularly of isopropyl ether, butyl oxide, hexyl oxide.

La réaction se fait généralement à une température voisine de 0°C.The reaction is generally carried out at a temperature close to 0 ° C.

La concentration en dérivé du phénol (produit de départ) est habituellement comprise entre 0,1 et 10 moles/l.The concentration of phenol derivative (starting product) is usually between 0.1 and 10 moles / l.

On utilise en général une quantité d'agent bromant comprise entre 0,8 et 1,2 équivalent de brome réactif.In general, an amount of brominating agent is used between 0.8 and 1.2 equivalent of reactive bromine.

La réaction se fait en principe en coulant l'agent bromant dans le mélange solvant-dérivé du phénol.The reaction is carried out in principle by pouring the brominating agent into the solvent-phenol derivative mixture.

Une fois la réaction terminée, on peut séparer le produit du milieu réactionnel par tout moyen connu après, le cas échéant, traitement classique pour le passage de sa forme sel à la forme recherchée. Un exemple de traitement consiste à ajouter une solution acide au milieu réactionnel et à augmenter la température afin d'hydrolyser le précipité formé au cours de la réaction.Once the reaction is complete, the product can be separated from the reaction medium by any known means after, if necessary, conventional treatment for the transition from its salt form to the desired form. An example of treatment consists in adding an acid solution to the reaction medium and in increasing the temperature in order to hydrolyze the precipitate formed during the reaction.

Un exemple concret mais non limitatif va maintenant être donné.A concrete but non-limiting example will now be given.

EXEMPLEEXAMPLE

Dans un ballon tricol de 100 ml muni d'un thermomètre, d'un réfrigérant relié à un barboteur contenant de la soude et du sulfite de sodium en solution aqueuse, d'une ampoule à brome, d'une agitation magnétique, on place :

  • . 7,25 g de gaïacol,
  • . 75 ml d'éther isopropylique.
In a 100 ml three-necked flask fitted with a thermometer, a condenser connected to a bubbler containing sodium hydroxide and sodium sulfite in aqueous solution, a dropping funnel, magnetic stirring, the following are placed:
  • . 7.25 g of guaiacol,
  • . 75 ml of isopropyl ether.

Le ballon est refroidi à 0°C, et en maintenant cette température, on ajoute goutte à goutte, par l'ampoule à brome, une solution de 6,75 g de N.N. dibromotertiobutylamine dans l'éther isopropylique.The flask is cooled to 0 ° C., and maintaining this temperature, a solution of 6.75 g of N.N. dibromotertiobutylamine in isopropyl ether is added dropwise through the dropping funnel.

3 heures après le début de l'addition, l'excès de brome réactif est détruit par une solution aqueuse de sulfite de sodium à 10 %, et 100 ml d'une solution d'acide sulfurique 2N sont ajoutés. Ce tout est porté à 50°C afin d'hydrolyser le précipité formé au cours de la réaction.3 hours after the start of the addition, the excess reactive bromine is destroyed by a 10% aqueous sodium sulfite solution, and 100 ml of a 2N sulfuric acid solution are added. This is brought to 50 ° C. in order to hydrolyze the precipitate formed during the reaction.

Après neutralisation, la phase organique est décantée, lavée et séchée.After neutralization, the organic phase is decanted, washed and dried.

Les résultats sont les suivants :
   taux de transformation du gaïacol : 80 %,
   rendement par rapport au produit transformé en bromo-6 gaïacol : 75 %,The results are as follows:
guaiacol transformation rate: 80%,
yield compared to the product transformed into bromo-6 guaiacol: 75%,

Bien entendu, l'invention n'est nullement limitée aux modes de réalisation décrits qui n'ont été donnés qu'à titre d'exemples. En particulier, elle comprend tous les moyens constituant des équivalents techniques des moyens décrits ainsi que leurs combinaisons si celles-ci sont mises en oeuvre dans le cadre de la protection comme revendiquée.Of course, the invention is in no way limited to the embodiments described which have been given only by way of examples. In particular, it includes all the means constituting technical equivalents of the means described as well as their combinations if these are used in the context of protection as claimed.

Claims (6)

1. Process for preparing an ortho-monobromo derivative of phenol, characterised in that a phenol derivative of formula:
Figure imgb0006
 in which X denotes OH or an alkoxy, CH₂OH, CHO or CO₂R radical, R being an alkyl, alkenyl or alkoxy radical, it being possible for these radicals to be linear or branched, or a cycloalkyl, cycloalkenyl, alkylcycloalkenyl, benzyl, amine, terpene or glycol radical, and R₁ and R₂ are identical or different and denote hydrogen, a halogen or an alkyl, acyl or alkoxy radical, and with the proviso that the position ortho to the OH is free, is reacted with a derivative of an amine possessing at least one N-Br bond.
2. Process according to claim 1, characterised in that the derivative of an amine precipitated is a derivative of an aliphatic amine, and more especially of an alkylamine.
3. Process according to claim 1 or 2, characterised in that a phenol derivative of formula (1) in which R₁ and R₂ are in the meta position is reacted.
4. Process according to one of claims 1 to 3, characterised in that a phenol derivative of formula (1) in which R₁ = R₂ = H is reacted.
5. Process according to one of claims 1 to 4, characterised in that a phenol derivative of formula (1) in which X is an alkoxy radical is reacted.
6. Process according to one of the preceding claims, characterised in that the reaction is conducted in a solvent chosen from the group comprising halogenated or unhalogenated aromatic hydrocarbons, ethers and halogenated aliphatic hydrocarbons.
EP89401027A 1988-04-22 1989-04-14 Process for the preparation of an ortho-substituted mono-brominated derivative of phenol Expired - Lifetime EP0338898B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT89401027T ATE78016T1 (en) 1988-04-22 1989-04-14 PROCESS FOR THE PREPARATION OF ORTHOSUBSTITUTED MONOBROMATED PHENOL DERIVATIVE.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR8805329 1988-04-22
FR8805329A FR2630436B1 (en) 1988-04-22 1988-04-22 PROCESS FOR THE PREPARATION OF A MONO-BROMINE DERIVATIVE IN ORTHO OF PHENOL

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EP0338898A1 EP0338898A1 (en) 1989-10-25
EP0338898B1 true EP0338898B1 (en) 1992-07-08

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EP (1) EP0338898B1 (en)
JP (1) JPH0272135A (en)
AT (1) ATE78016T1 (en)
DE (1) DE68902000T2 (en)
ES (1) ES2033103T3 (en)
FR (1) FR2630436B1 (en)
GR (1) GR3005883T3 (en)
IE (1) IE891301L (en)
IL (1) IL89986A0 (en)

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US5756851A (en) * 1996-10-21 1998-05-26 Albemarle Corporation Production of nabumetone or precursors thereof

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US4182912A (en) * 1978-09-14 1980-01-08 Polaroid Corporation Synthesis of 5-bromopyrogallol 1,3-dimethyl ether
IL74775A (en) * 1985-04-01 1988-08-31 Imi Tami Institute Research Method for the manufacture of mixtures of 3-phenoxybenzyl bromide and 3-phenoxybenzal bromide

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IL89986A0 (en) 1989-12-15
ATE78016T1 (en) 1992-07-15
DE68902000T2 (en) 1993-02-04
DE68902000D1 (en) 1992-08-13
EP0338898A1 (en) 1989-10-25
FR2630436A1 (en) 1989-10-27
FR2630436B1 (en) 1990-07-27
IE891301L (en) 1989-10-22
ES2033103T3 (en) 1993-03-01
JPH0272135A (en) 1990-03-12
GR3005883T3 (en) 1993-06-07

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